Ling Li1,2, Mei-Ying Shao1, Shu-Cheng Zou2, Zhe-Feng Xiao3, Zhu-Chu Chen4. 1. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, 410008, Hunan, People's Republic of China. 2. Department of Neurosurgery, Brain Hospital of Hunan Province, Changsha, 410008, People's Republic of China. 3. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, 410008, Hunan, People's Republic of China. xiaozf@csu.edu.cn. 4. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, 410008, Hunan, People's Republic of China. chenzhuchu@126.com.
Abstract
BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS: MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.
BACKGROUND:Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS:MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.